tbuckley/cabot-search huggingface dataset:
Angiopoietin-2 blockade suppresses growth of liver metastases from pancreatic neuroendocrine tumors by promoting T cell recruitment
Authors: Eunhyeong Lee, Sophie O'Keefe, Alessandra Leong, Ha-Ram Park, Janani Varadarajan, Subrata Chowdhury, Shannon Hiner, Sungsoo Kim, Anahita Shiva, Richard A Friedman, Helen Remotti, Tito Fojo, Hee Won Yang, Gavin Thurston, Minah Kim
Journal: Journal of Clinical Investigation (2023)

Improving the management of metastasis in pancreatic neuroendocrine tumors (PanNETs) is critical, as nearly half of patients with PanNETs present with liver metastases, and this accounts for the majority of patient mortality. We identified angiopoietin-2 (ANGPT2) as one of the most upregulated angiogenic factors in RNA-Seq data from human PanNET liver metastases and found that higher ANGPT2 expression correlated with poor survival rates. Immunohistochemical staining revealed that ANGPT2 was localized to the endothelial cells of blood vessels in PanNET liver metastases. We observed an association between the upregulation of endothelial ANGPT2 and liver metastatic progression in both patients and transgenic mouse models of PanNETs. In human and mouse PanNET liver metastases, ANGPT2 upregulation coincided with poor T cell infiltration, indicative of an immunosuppressive tumor microenvironment. Notably, both pharmacologic inhibition and genetic deletion of ANGPT2 in PanNET mouse models slowed the growth of PanNET liver metastases. Furthermore, pharmacologic inhibition of ANGPT2 promoted T cell infiltration and activation in liver metastases, improving the survival of mice with metastatic PanNETs. These changes were accompanied by reduced plasma leakage and improved vascular integrity in metastases. Together, these findings suggest that ANGPT2 blockade may be an effective strategy for promoting T cell infiltration and immunostimulatory reprogramming to reduce the growth of liver metastases in PanNETs.
Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial
Authors: Thomas A. Wadden, Ariana M. Chao, Sriram Machineni, Robert Kushner, Jamy Ard, Gitanjali Srivastava, Bruno Halpern, Shuyu Zhang, Jiaxun Chen, Mathijs C. Bunck, Nadia N. Ahmad, Tammy Forrester
Journal: Nature Medicine (2023)

Abstract The effects of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, on weight reduction after successful intensive lifestyle intervention are unknown. This double-blind, placebo-controlled trial randomized (1:1) adults with body mass index ≥30 or ≥27 kg/m 2 and at least one obesity-related complication (excluding diabetes), who achieved ≥5.0% weight reduction after a 12-week intensive lifestyle intervention, to tirzepatide maximum tolerated dose (10 or 15 mg) or placebo once weekly for 72 weeks ( n = 579). The treatment regimen estimand assessed effects regardless of treatment adherence in the intention-to-treat population. The coprimary endpoint of additional mean per cent weight change from randomization to week 72 was met with changes of −18.4% (standard error (s.e.) 0.7) with tirzepatide and 2.5% (s.e. 1.0) with placebo (estimated treatment difference −20.8 percentage points (95% confidence interval (CI) −23.2%, −18.5%; P &lt; 0.001). The coprimary endpoint of the percentage of participants achieving additional weight reduction ≥5% was met with 87.5% (s.e. 2.2) with tirzepatide and 16.5% (s.e. 3.0) with placebo achieving this threshold (odds ratio 34.6%; 95% CI 19.2%, 62.6%; P &lt; 0.001). The most common adverse events with tirzepatide were gastrointestinal, with most being mild to moderate in severity. Tirzepatide provided substantial additional reduction in body weight in participants who had achieved ≥5.0% weight reduction with intensive lifestyle intervention. ClinicalTrials.gov registration: NCT04657016 .
Co‐targeting FAK and Gli1 inhibits the tumor‐associated macrophages‐released CCL22‐mediated esophageal squamous cell carcinoma malignancy
Authors: Jie Chen, Yanmeng Zhu, Di Zhao, Lingyuan Zhang, Jing Zhang, Yuanfan Xiao, Qingnan Wu, Yan Wang, Qimin Zhan
Journal: MedComm (2023)

Esophageal squamous cell carcinoma (ESCC) is a frequently seen esophageal tumor type in China. Activation of signaling proteins and relevant molecular mechanisms in ESCC are partially explored, impairing the antitumor efficiency of targeted therapy in ESCC treatment. Tumor-associated macrophages (TAMs)-released C-C motif chemokine 22 (CCL22) can activate intratumoral focal adhesion kinase (FAK), thus promoting the progression of ESCC. Here, we demonstrated that highly secreted CCL22 by TAMs (CCL22-positive TAMs) induced ESCC cell stemness and invasion through facilitating transcriptional activity of intratumoral glioma-associated oncogene 1 (Gli1), a downstream effector for Hedgehog (HH) pathway. Mechanistically, FAK-activated protein kinase B (AKT) mediated Gli1 phosphorylation at its Ser
Corrigendum to “PEGylated fullerene/iron oxide nanocomposites for photodynamic therapy, targeted drug delivery and MR imaging” [Biomaterials 34 (2013) 9666–9677/ pubmed: 24034498]
Authors: Jinjin Shi, Xiaoyuan Yu, Lei Wang, Yan Liu, Jun Gao, Jing Zhang, Rou Ma, Ruiyuan Liu, Zhenzhong Zhang
Journal: Biomaterials (2023)
Injectable Living Probiotic Dressing Built by Droplet‐Based Microfluidics and Photo‐Cross‐Linking to Prevent Pathogenic Infection and Promote Wound Repair
Authors: Yunyun Wei, Ziqiang Han, Xiaolong Mao
Journal: Advanced Healthcare Materials (2023)

Abstract The treatment of infected wounds faces great challenges due to the emergence of antibiotic resistance and the lack of persistence in drug release. Here, a living probiotic dressing is constructed by integrating droplet‐shearing and photo‐cross‐linking. Saccharomyces boulardii ( S. boulardii ), the only probiotic used clinically, is encapsulated and attached to a wound under light irradiation. A double‐layer hydrogel provides a protective barrier for cell growth and proliferation while preventing the escape of S. boulardii . The living probiotic dressing shows superior biosafety with fibroblast cells. Strikingly, in vitro and in vivo experiments indicate that the living probiotic dressing not only inhibits bacterial survival and colonization, but also alleviates inflammation and accelerates wound closure. More significantly, the living probiotic dressing promotes collagen deposition and neovascularization, which accelerates wound healing. This work can provide new ideas for clinical wound treatment and widen the application of probiotics in tissue engineering.
De Novo Design of Near‐Infrared Fluorescent Agents Activated by Peroxynitrite and Glutathione‐Responsive Imaging for Diabetic Liver Disease
Authors: Renfeng Jiang, Hongshuai Zhang, Qian Liu, Xuefeng Yang, Longwei He, Lin Yuan, Dan Cheng
Journal: Advanced Healthcare Materials (2023)

Abstract Diabetes and its complications, such as diabetes liver disease, is a major problem puzzling people's health. The detection of redox states in its pathological process can effectively help us gain a deeper understanding of the disease. The pair of oxidation–reduction substances peroxynitrite (ONOO − ) and glutathione (GSH) is considered to be closely related to their occurrence and development. Thus, direct visualization of ONOO − and GSH in diabetes liver disease is critical to evaluate the disease at the molecular level. Herein, two activatable agents NTCF‐ONOO − and NTCF‐GSH are prepared for selectively detecting ONOO − and GSH through protection and deprotection strategies based on hydroxyl and amino groups of near‐infrared fluorophore. Fluorescence imaging of exogenous and endogenous ONOO − and GSH changes in living cells and in vivo is observed. The ONOO − and GSH level in the diabetes liver disease cellular model are visualized and the possible redox imbalance mechanism related to the oxidized (NAD + ) and reduced (NADH) nicotinamide adenine dinucleotides is explored in this process. Moreover, these probes can sensitively recognize ONOO − and GSH in the process of oxidative stress resulting from streptozotocin and streptozotocin/acetaminophen‐induced complex diabetic liver disease in vivo. In addition, they can be applied for monitoring the clinical serum sample related with diabetic patients.
Incorrect Date in Figure 1
Journal: JAMA Network Open (2023)

Lei Yan, PhD; Elani Streja, PhD; Yuli Li, MS; Nallakkandi Rajeevan, PhD; Mazhgan Rowneki, MPH; Kristin Berry, PhD; Denise M. Hynes, MPH, PhD, RN; Francesca Cunningham, PharmD; Grant D. Huang, MPH, PhD; Mihaela Aslan, PhD; George N. Ioannou, BMBCh, MS; Kristina L. Bajema, MD, MSc
Early Childhood Education and Midlife Ideal Cardiovascular Health in a Prospective Urban Cohort
Authors: Arthur J. Reynolds, Nishank Varshney, Suh-Ruu Ou, Rachel Kritzik, Marley Loveman-Brown
Journal: JAMA Pediatrics (2023)

This cohort study assesses whether preschool is associated with long-term cardiovascular health as measured by the American Heart Association’s Ideal Cardiovascular Health Index.
Super-small zwitterionic micelles enable the improvement of blood-brain barrier crossing for efficient orthotopic glioblastoma combinational therapy
Authors: Ke Wang, Bingbing Zhao, Yuli Ao, Jinyu Zhu, Changshun Zhao, Wei Wang, Yan Zou, Dechun Huang, Yinan Zhong, Wei Chen, Hongliang Qian
Journal: Journal of Controlled Release (2023)
<i>Parvimonas micra</i> , an oral pathobiont associated with colorectal cancer, epigenetically reprograms human colonocytes
Authors: Emma Bergsten, Denis Mestivier, Francoise Donnadieu, Thierry Pedron, Caroline Barau, Landry Tsoumtsa Meda, Amel Mettouchi, Emmanuel Lemichez, Olivier Gorgette, Mathias Chamaillard, Amaury Vaysse, Stevenn Volant, Abiba Doukani, Philippe J. Sansonetti, Iradj Sobhani, Giulia Nigro
Journal: Gut Microbes (2023)

Recently, an intestinal dysbiotic microbiota with enrichment in oral cavity bacteria has been described in colorectal cancer (CRC) patients. Here, we characterize and investigate one of these oral pathobionts, the Gram-positive anaerobic coccus
Variations in State Laws on Mental Health–Related Firearm Prohibition
Authors: Deirdre M. Bowen, Ali Rowhani-Rahbar, Alexander McCourt, Marian Betz, Frederick P. Rivara
Journal: JAMA Internal Medicine (2023)

This quality improvement study assesses heterogeneity in state rules regarding reporting of mental health conditions to the National Instant Criminal Background Check System when individuals seek to acquire firearms.
Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans: report of an expert meeting
Authors: Jun Sun, M. Nedim Ince, Clara Abraham, Terrence Barrett, Lisa A. Brenner, Yingzi Cong, Reza Dashti, Pradeep K. Dudeja, David Elliott, Thomas S. Griffith, Peter S. Heeger, Andrew Hoisington, Kaikobad Irani, Tae Kon Kim, Neeraj Kapur, Joseph Leventhal, Mansour Mohamadzadeh, Ece Mutlu, Rodney Newberry, Jonathan U. Peled, Israel Rubinstein, Salyka Sengsayadeth, Chen Sabrina Tan, Xiao-Di Tan, Eric Tkaczyk, Jason Wertheim, Zheng Jenny Zhang
Journal: Gut Microbes (2023)

The present report summarizes the United States Department of Veterans Affairs (VA) field-based meeting titled "Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans." Our Veteran patient population experiences a high incidence of service-related chronic physical and mental health problems, such as infection, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), various forms of hematological and non-hematological malignancies, neurologic conditions, end-stage organ failure, requiring transplantation, and posttraumatic stress disorder (PTSD). We report the views of a group of scientists who focus on the current state of scientific knowledge elucidating the mechanisms underlying the aforementioned disorders, novel therapeutic targets, and development of new approaches for clinical intervention. In conclusion, we dovetailed on four research areas of interest: 1) microbiome interaction with immune cells after hematopoietic cell and/or solid organ transplantation, graft-versus-host disease (GVHD) and graft rejection, 2) intestinal inflammation and its modification in IBD and cancer, 3) microbiome-neuron-immunity interplay in mental and physical health, and 4) microbiome-micronutrient-immune interactions during homeostasis and infectious diseases. At this VA field-based meeting, we proposed to explore a multi-disciplinary, multi-institutional, collaborative strategy to initiate a roadmap, specifically focusing on host microbiome-immune interactions among those with service-related chronic diseases to potentially identify novel and translatable therapeutic targets.
Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
Authors: Raphael Koch, Lianne Haveman, Ruth Ladenstein, Benedicte Brichard, Heribert Jürgens, Sona Cyprova, Henk van den Berg, Wolf Hassenpflug, Anna Raciborska, Torben Ek, Daniel Baumhoer, Gerlinde Egerer, Leo Kager, Marleen Renard, Peter Hauser, Stefan Burdach, Judith V.M.G. Bovee, Angela M. Hong, Peter Reichardt, Jarmila Kruseova, Arne Streitbürger, Thomas Kühne, Torsten Kessler, Marie Bernkopf, Trude Butterfaß-Bahloul, Catharina Dhooge, Sebastian Bauer, János Kiss, Michael Paulussen, Fiona Bonar, Andreas Ranft, Beate Timmermann, Jelena Rascon, Volker Vieth, Jukka Kanerva, Andreas Faldum, Wolfgang Hartmann, Lars Hjorth, Vivek A. Bhadri, Markus Metzler, Hans Gelderblom, Uta Dirksen
Journal: Clinical Cancer Research (2023)

The phase III, open-label, prospective, multicenter, randomized Ewing 2008R1 trial (EudraCT2008-003658-13) was conducted in 12 countries to evaluate the effect of zoledronic acid (ZOL) maintenance therapy compared with no add-on regarding event-free survival (EFS, primary endpoint) and overall survival (OS) in standard-risk Ewing sarcoma (EWS).
Changes in Care Use and Financial Status Associated With Dementia in Older Adults
Authors: HwaJung Choi, Kenneth M. Langa, Edward C. Norton, Tsai-Chin Cho, Cathleen M Connell
Journal: JAMA Internal Medicine (2023)

Importance Estimating the effects of dementia on care use and financial outcomes is timely, as the population with dementia will more than double in the next few decades. Objective To determine the incremental changes associated with dementia in regard to older adults’ care use and assess financial consequences for individuals, families, and society. Design, Setting, and Participants This population-based cohort study included propensity score matching on national, longitudinal data using extensive baseline variables of sociodemographic characteristics, economic status, family availability, health conditions, disability status, and outpatient care use among 2 groups of US adults aged 55 years or older who did not have dementia. In total, 2387 adults experienced the onset of dementia during the 2-year follow-up (dementia group) and 2387 adults did not (control group). Participants were followed up for 8 years from the baseline. Data were analyzed from February 2021 to August 2023. Exposure Dementia determined based on Langa-Weir classification. Main Outcomes and Measures Outcomes of care use included monthly care hours from family and unpaid helpers, in-home medical services, hospital stay, and nursing facility stay. Financial outcomes included out-of-pocket medical costs, wealth, and the status of having Medicaid. Results Among the full sample, the mean (SD) age was 75.4 [10.4] years, and 59.7% of participants were female. Care use was similar at baseline between the matched groups but was substantially greater for the dementia group vs control group in subsequent years, especially during the 2-year follow-up: 45 vs 13 monthly care hours from family and unpaid helpers, 548 of 2370 participants (23.1%) vs 342 of 2383 (14.4%) using in-home medical care, 1104 of 2369 (46.6%) vs 821 of 2377 (34.5%) with hospital stay, and 489 of 2375 (20.6%) vs 104 of 2384 (4.4%) using a nursing facility. The increase in use of a nursing facility was especially high if baseline family care availability was low. Over the 8-year follow-up in the dementia group, the 2-year out-of-pocket medical costs increased from $4005 to $10 006, median wealth was reduced from $79 339 to $30 490, and those enrolling in Medicaid increased from 379 of 2358 participants (16.1%) to 201 of 676 participants (29.7%). No statistically significant changes in financial outcomes were found in the control group. Conclusion and Relevance This cohort study demonstrated that the incremental changes associated with dementia in regard to older adults’ long-term care and financial burden are substantial. Family care availability should be accounted for in a comprehensive assessment of predicting the effects of dementia.
<i>Prdm16</i> mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators
Authors: Jirko Kühnisch, Simon Theisen, Josephine Dartsch, Raphaela Fritsche-Guenther, Marieluise Kirchner, Benedikt Obermayer, Anna Bauer, Anne-Karin Kahlert, Michael Rothe, Dieter Beule, Arnd Heuser, Philipp Mertins, Jennifer A Kirwan, Nikolaus Berndt, Calum A MacRae, Norbert Hubner, Sabine Klaassen
Journal: Cardiovascular Research (2023)

Abstract Aims Mutation of the PRDM16 gene causes human dilated and non-compaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with post-natal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. Methods and results This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN. Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt cardiac tissue of both sexes showed reductions in metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and the tricarboxylic acid cycle. Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. An accumulation of triacylglycerides exclusively in male Prdm16csp1/wt hearts suggests a sex-specific metabolic adaptation. Metabolic modelling using CARDIOKIN identified a reduction in fatty acid utilization in males as well as lower glucose utilization in female Prdm16csp1/wt cardiac tissue. On the level of transcripts and protein expression, Prdm16csp1/wt hearts demonstrate an up-regulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre-B-cell leukaemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional up-regulation was detected for Prdm16 itself, probably through an autoregulatory mechanism. Conclusions Monoallelic, global Prdm16 mutation diminishes cardiac performance in Prdm16csp1/wt mice. Metabolic alterations and transcriptional dysregulation in Prdm16csp1/wt affect cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype, indicating sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in the PRDM16 associated cardiac pathology.
Incorrect Institution Name in Author Affiliations
Journal: JAMA Network Open (2023)

Satoshi Funada, MD, PhD; Takashi Yoshioka, MD, PhD; Yan Luo, MD, PhD; Toshi Iwama, PhD; Chikako Mori, MS; Naofumi Yamada, MS; Hideki Yoshida, PhD; Kota Katanoda, PhD; Toshi A. Furukawa, MD, PhD
A Dose‐Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration
Authors: Junlong Tan, Shuang Li, Chaoyang Sun, Guo Bao, Meijing Liu, Zehao Jing, Hanwei Fu, Yanhua Sun, Qingmin Yang, Yufeng Zheng, Xiaogang Wang, Hongtao Yang
Journal: Advanced Healthcare Materials (2023)

Abstract Zinc (Zn) plays a crucial role in bone metabolism and imbues biodegradable Zn‐based materials with the ability to promote bone regeneration in bone trauma. However, the impact of Zn biodegradation on bone repair, particularly its influence on angiogenesis, remains unexplored. This study reveals that Zn biodegradation induces a consistent dose‐dependent spatiotemporal response in angiogenesis,both in vivo and in vitro. In a critical bone defect model, an increase in Zn release intensity from day 3 to 10 post‐surgery is observed. By day 10, the CD31‐positive area around the Zn implant significantly surpasses that of the Ti implant, indicating enhanced angiogenesis. Furthermore,angiogenesis exhibits a distance‐dependent pattern closely mirroring the distribution of Zn signals from the implant. In vitro experiments demonstrate that Zn extraction fosters the proliferation and migration of human umbilical vein endothelial cells and upregulates the key genes associated with tube formation, such as HIF‐1α and VEGF‐A, peaking at a concentration of 22.5 µM. Additionally, Zn concentrations within the range of 11.25−45 µM promote the polarization of M0‐type macrophages toward the M2‐type, while inhibiting polarization toward the M1‐type. These findings provide essential insights into the biological effects of Zn on bone repair, shedding light on its potential applications.
CD8+ lymphocytes are critical for early control of tuberculosis in macaques
Authors: Caylin G. Winchell, Sarah K. Nyquist, Michael C. Chao, Pauline Maiello, Amy J. Myers, Forrest Hopkins, Michael Chase, Hannah P. Gideon, Kush V. Patel, Joshua D. Bromley, Andrew W. Simonson, Roisin Floyd-O’Sullivan, Marc Wadsworth, Jacob M. Rosenberg, Rockib Uddin, Travis Hughes, Ryan J. Kelly, Josephine Griffo, Jaime Tomko, Edwin Klein, Bonnie Berger, Charles A. Scanga, Joshua Mattila, Sarah M. Fortune, Alex K. Shalek, Philana Ling Lin, JoAnne L. Flynn
Journal: The Journal of Experimental Medicine (2023)

The functional role of CD8+ lymphocytes in tuberculosis remains poorly understood. We depleted innate and/or adaptive CD8+ lymphocytes in macaques and showed that loss of all CD8α+ cells (using anti-CD8α antibody) significantly impaired early control of Mycobacterium tuberculosis (Mtb) infection, leading to increased granulomas, lung inflammation, and bacterial burden. Analysis of barcoded Mtb from infected macaques demonstrated that depletion of all CD8+ lymphocytes allowed increased establishment of Mtb in lungs and dissemination within lungs and to lymph nodes, while depletion of only adaptive CD8+ T cells (with anti-CD8β antibody) worsened bacterial control in lymph nodes. Flow cytometry and single-cell RNA sequencing revealed polyfunctional cytotoxic CD8+ lymphocytes in control granulomas, while CD8-depleted animals were unexpectedly enriched in CD4 and γδ T cells adopting incomplete cytotoxic signatures. Ligand-receptor analyses identified IL-15 signaling in granulomas as a driver of cytotoxic T cells. These data support that CD8+ lymphocytes are required for early protection against Mtb and suggest polyfunctional cytotoxic responses as a vaccine target.